Cancer Conference Update: A Multimedia Review of Key Presentations from the 2016 American Society of Hematology Annual MeetingAbstract 976: A Phase II trial of elotuzumab, lenalidomide and dexamethasone in high-risk smoldering MM
4:19 minutes.
TRANSCRIPTION:
DR MIKHAEL: This is, of course, an area of controversy in the myeloma world. It’s, I think, an important area to understand more. I think right now the myeloma community has preferred to say, “Let’s continue to adjust the definition of myeloma so that we only treat active myeloma,” and, as it were, cream off the top of smoldering, like we did when the criteria was made to add the 3 new criteria of 60% plasma cells, light chains greater than 100 involved over uninvolved and MRI findings. But there’s still a second modality of thinking, of saying, “Okay. That’s true. You can redefine myeloma to cream the top off, but there is still a group of smoldering patients who we’re not really sure what to do with.” And that high-risk smoldering group, if you will, the ultrahigh-risk smoldering group are now true myeloma. So you treat them. What can we do with that high-risk smoldering group? And I always approach this with a bit of caution, because I don’t want to undertreat someone who really has myeloma. But could there be a way to less aggressively but significantly treat that high-risk group and never let them get to myeloma? That would be a great option, wouldn’t it? Now, we have to be careful with that kind of thinking to not backtrack all the way into, let’s say, monoclonal gammopathy of undetermined significance, where 5% of adults have it. But this study was really just looking, I think, at the feasibility and the initial outcomes in about 40 patients with high-risk smoldering myeloma. I think the message to the community oncologists is that we’re not treating smoldering myeloma in clinical practice right now. We are still trying to evaluate whether or not they need treatment. And studies like this will help us. But if a patient meets those criteria that upgrade them to true myeloma, then they should be treated like a myeloma patient. But smoldering myeloma we’re still trying to figure out if we should treat them or not. DR LOVE: And, I mean, I remember seeing a series looking at KRd in, quote, smoldering myeloma. But what do you make out of this study? What does it mean, I mean, elotuzumab/len and dex in terms of what they saw? I mean, you wouldn’t use elotuzumab/len and dex as up-front treatment of myeloma. DR MIKHAEL: Right. And that’s why I approach this abstract, respectfully, with caution, is, I don’t think it’s going to change what we do. I think it’s an uncharted territory of should we treat high-risk smoldering or not? And based on some of the work in the lab and the synergy between elotuzumab and lenalidomide, could there be a chance that this would be a sweet spot of not very toxic therapy but enough therapy to really arrest smoldering at that level and never move on to active? I’m not sure that’s going to be the long-term outcome. But it’s worth at least exploring. DR LOVE: I think, or maybe I dreamed this, that there was some trial that included dara for smoldering myeloma. DR MIKHAEL: There wasn’t one presented at ASH, but I know that there are some that are in development. Following up on Ola Landgren’s work with KRd in the smoldering world. There’s some who even want to look at dara/KRd or dara/Rd or dara/bortezomib/dex, all those combinations. And again, I have to confess my bias here, Neil, that I’m a little hesitant in that. I would rather us better predict who is going — and the analogy I use is, if I see you as my friend Neil Love walking towards a cliff, do I have to wait until you’re falling off the cliff to know you’re in trouble? Of course not. But if the cliff is 5 miles away and it’s a nice sunny day in Miami and there’s no need to pull you back, I won’t. But what we want to know is, how fast is Neil running and how close is Neil to the edge? And, clearly, those 3 new features are evidence of that. But I suspect that we will add other features with time. And I’d almost rather do that than perhaps treat the smoldering group. But I think the other camp’s philosophy of maybe treating someone who is more than MGUS but less than myeloma to see if we cannot just sit and wait and watch on them but actually change the natural course of smoldering myeloma is at least worth exploring. |